508 research outputs found

    Carbon contamination topography analysis of EUV masks

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    The impact of carbon contamination on extreme ultraviolet (EUV) masks is significant due to throughput loss and potential effects on imaging performance. Current carbon contamination research primarily focuses on the lifetime of the multilayer surfaces, determined by reflectivity loss and reduced throughput in EUV exposure tools. However, contamination on patterned EUV masks can cause additional effects on absorbing features and the printed images, as well as impacting the efficiency of cleaning process. In this work, several different techniques were used to determine possible contamination topography. Lithographic simulations were also performed and the results compared with the experimental data

    Synthesis of fluorosugar reagents for the construction of well-defined fluoroglycoproteins.

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    2-Deoxy-2-fluoroglycosyl iodides are privileged glycosyl donors for the stereoselective preparation of 1-Nu-β-fluorosugars, which are useful reagents for chemical site-selective protein glycosylation. Ready access to such β-fluorosugars enables the mild and efficient construction of well-defined fluoroglycoproteins.We thank the European Commission (Marie Curie CIG, O.B. and G.J.L.B.), MICINN, Spain (Juan de la Cierva Fellowship, O.B.), MINECO, Spain (CTQ2011-22872BQU) and Generalitat de Catalunya (M.S.) for generous financial support. We also thank Mr. Adrià Cardona-Benages (URV) for technical assis-tance. G.J.L.B. thanks the Royal Society (University Research Fellowship), Fundação para a Ciência a Tecnologia, Portugal (FCT Investigator), and the EPSRC for funding.This is the final version of the article. It first appeared from ACS via http://pubs.acs.org/doi/abs/10.1021/acs.orglett.5b01259

    Experimental limits on nucleon decay and ΔB=2 processes

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    Results from the IMB collabration to detect possible proton decay in a salt mine near Cleveland, Ohio are presented. Detection apparatus is described.(AIP)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87900/2/1_1.pd

    The Herpes Simplex Virus-1 Transactivator Infected Cell Protein-4 Drives VEGF-A Dependent Neovascularization

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    Herpes simplex virus-1 (HSV-1) causes lifelong infection affecting between 50 and 90% of the global population. In addition to causing dermal lesions, HSV-1 is a leading cause of blindness resulting from recurrent corneal infection. Corneal disease is characterized by loss of corneal immunologic privilege and extensive neovascularization driven by vascular endothelial growth factor-A (VEGF-A). In the current study, we identify HSV-1 infected cells as the dominant source of VEGF-A during acute infection, and VEGF-A transcription did not require TLR signaling or MAP kinase activation. Rather than being an innate response to the pathogen, VEGF-A transcription was directly activated by the HSV-1 encoded immediate early transcription factor, ICP4. ICP4 bound the proximal human VEGF-A promoter and was sufficient to promote transcription. Transcriptional activation also required cis GC-box elements common to the VEGF-A promoter and HSV-1 early genes. Our results suggest that the neovascularization characteristic of ocular HSV-1 disease is a direct result of HSV-1's major transcriptional regulator, ICP4, and similarities between the VEGF-A promoter and those of HSV-1 early genes

    The search for proton decay

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    Following a very brief description of the theoretical developments which motivated the search for proton decay, I shall describe one of these experiments (the IMB experiment) in some detail. Then I shall compare recent results from that experiment with those from other detectors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87399/2/321_1.pd

    IMB Detector‐The first 30 Days

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    A large water Chernekov detector, located 2000 feet below ground, has recently been turned on. The primary purpose of the device is to measure nucleon stability to limits 100 times better than previous measurements. The properties of the detector are described along with its operating characteristics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87428/2/138_1.pd

    Potent antitumoral activity of TRAIL through generation of tumor-targeted single-chain fusion proteins

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    In an attempt to improve TRAIL's (tumor necrosis factor-related apoptosis-inducing ligand) tumor selective activity a variant was designed, in which the three TRAIL protomers are expressed as a single polypeptide chain (scTRAIL). By genetic fusion with a single-chain antibody fragment (scFv) recognizing the extracellular domain of ErbB2, we further equipped scTRAIL with tumor-targeting properties. We studied tumor targeting and apoptosis induction of scFv–scTRAIL in comparison with non-targeted scTRAIL. Importantly, the tumor antigen-targeted scTRAIL fusion protein showed higher apoptotic activity in vitro, with a predominant action by TRAIL-R2 signaling. Pharmacokinetic studies revealed increased plasma half-life of the targeted scTRAIL fusion protein compared with scTRAIL. In vivo studies in a mouse tumor model with xenotransplanted Colo205 cells confirmed greater response to the ErbB2-specific scTRAIL fusion protein compared with non-targeted scTRAIL both under local and systemic application regimen. Together, in vitro and in vivo data give proof of concept of higher therapeutic activity of tumor-targeted scFv–scTRAIL molecules. Further, we envisage that through targeting of scTRAIL, potential side effects should be minimized. We propose that scFv-mediated tumor targeting of single-chain TRAIL represents a promising strategy to improve TRAIL's antitumoral action and to minimize potential unwanted actions on normal tissues

    Transcriptome Analysis of the Arabidopsis Megaspore Mother Cell Uncovers the Importance of RNA Helicases for Plant Germline Development

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    Germ line specification is a crucial step in the life cycle of all organisms. For sexual plant reproduction, the megaspore mother cell (MMC) is of crucial importance: it marks the first cell of the plant “germline” lineage that gets committed to undergo meiosis. One of the meiotic products, the functional megaspore, subsequently gives rise to the haploid, multicellular female gametophyte that harbours the female gametes. The MMC is formed by selection and differentiation of a single somatic, sub-epidermal cell in the ovule. The transcriptional network underlying MMC specification and differentiation is largely unknown. We provide the first transcriptome analysis of an MMC using the model plant Arabidopsis thaliana with a combination of laser-assisted microdissection and microarray hybridizations. Statistical analyses identified an over-representation of translational regulation control pathways and a significant enrichment of DEAD/DEAH-box helicases in the MMC transcriptome, paralleling important features of the animal germline. Analysis of two independent T-DNA insertion lines suggests an important role of an enriched helicase, MNEME (MEM), in MMC differentiation and the restriction of the germline fate to only one cell per ovule primordium. In heterozygous mem mutants, additional enlarged MMC-like cells, which sometimes initiate female gametophyte development, were observed at higher frequencies than in the wild type. This closely resembles the phenotype of mutants affected in the small RNA and DNA-methylation pathways important for epigenetic regulation. Importantly, the mem phenotype shows features of apospory, as female gametophytes initiate from two non-sister cells in these mutants. Moreover, in mem gametophytic nuclei, both higher order chromatin structure and the distribution of LIKE HETEROCHROMATIN PROTEIN1 were affected, indicating epigenetic perturbations. In summary, the MMC transcriptome sets the stage for future functional characterization as illustrated by the identification of MEM, a novel gene involved in the restriction of germline fate

    Interleukin-7 Influences FOXP3+CD4+ Regulatory T Cells Peripheral Homeostasis

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    Mechanisms governing peripheral CD4+ FOXP3+ regulatory T cells (Treg) survival and homeostasis are multiple suggesting tight and complex regulation of regulatory T cells homeostasis. Some specific factors, such as TGF-β, interleukin-2 (IL-2) and B7 costimulatory molecules have been identified as essentials for maintenance of the peripheral Treg compartment. Conversely, Treg dependency upon classical T cell homeostatic factors such as IL-7 is still unclear. In this work, we formally investigated the role of IL-7 in Treg homeostasis in vivo in murine models. We demonstrated that IL-7 availability regulated the size of peripheral Treg cell pool and thus paralleled the impact of IL-7 on conventional T cell pool. Moreover, we showed that IL-7 administration increased Treg cell numbers by inducing thymic-independent Treg peripheral expansion. Importantly the impact of IL-7 on Treg expansion was detected whether conventional T cells were present or absent as IL-7 directly participates to the peripheral expansion of Treg after adoptive transfer into lymphopenic hosts. Our results definitively identify IL-7 as a central factor contributing to Treg peripheral homeostasis, thus reassembling Treg to other T cell subsets in respect of their need for IL-7 for their peripheral maintenance
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